A single dose, 4-way crossover, double-blind, placebo-controlled, randomized study to investigate the effect of JNJ-42847922 on polysomnography (PSG) measures in subjects with major depressive disorder with insomnia who are stably treated with antidepressants.

Completed

Conditions: Depression
Insomnia
10027946

Registration Number: NL-OMON40706

Lead Sponsor: Janssen-Cilag

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 10

Inclusion Criteria

1. Subjects must be men or women, 18 to 64 years of age, inclusive.
2. Body Mass Index (BMI) between 18 and 30 kg/m2 inclusive (BMI=weight/height2)
3. Subjects must be healthy / medically stable on the basis of clinical laboratory tests
performed at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, retesting of an abnormal lab value(s) that may lead to exclusion will be allowed once during the screening phase.
-The subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator.
4. Population specific:
• Subjects with a current/recurrent or past episode of MDD as established per Mini International Neuropsychiatric Interview (M.I.N.I.) at screening or otherwise specified by the treating physician.
• HAMD17 <= 21 (i.e., subjects with more than moderate depression will be excluded from study participation).
• Stably treated with SSRI/SNRI monotherapy, with no change in dose in the last 30 days before screening.
• Insomnia per PSG (latency to sleep onset > 20 minutes). Sleep onset latency measurements twice obtained during the screening period should be both > 20 min.
5. Before randomization, a woman must be either:
• Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 12 months, or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level >40 IU/L); permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy
• Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly): e.g., established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject). Women must agree to continue using these methods of contraception throughout the study and for at least 3 months after receiving the last dose of study medication.
Note: If the childbearing potential changes after start of the study (e.g., woman who is not heterosexually active becomes active) a woman must begin a highly effective method of birth control, as described above.
6. A woman of childbearing potential must have a negative urine pregnancy test at Screening and predose on Day 1 of each study period.
7. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after receiving the last dose of study drug.
8. A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must a

Exclusion Criteria

1. Subject has current signs/symptoms of, liver or renal insufficiency; hypothyroidism or hyperthyroidism (a normal thyroid-stimulating hormone [TSH] is required at screening; subjects with hypo- or hyperthyroidism who are on stable treatment with normal TSH may participate), significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances. Subjects with non-insulin dependent diabetes mellitus who are adequately controlled (not on insulin) may participate in the study.
2. Has uncontrolled hypertension (SBP >= 160 mmHg or DBP >= 90 mmHg despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment) at Screening and Day 1 prior to randomization; or any past history of hypertensive crisis.
3. Subject has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence).
4. Has a primary Diagnostic and Statistical Manual of Mental Disorders (4th edition) DSM-IV diagnosis of current (active) GAD, panic disorder, OCD, posttraumatic stress disorder (PTSD), anorexia nervosa, or bulimia nervosa. Subjects with primary depression with comorbid anxiety disorder, GAD, or PTSD are not excluded.
5. Has a current diagnosis of a psychotic disorder, MDD with psychosis, bipolar disorder, mental retardation, or cluster B personality disorder (e.g., borderline personality disorders, antisocial personality disorder).
6. Has suicidal ideation with some intent to act, or has homicidal ideation/intent, per Principal Investigator*s clinical judgment.
7. Abnormal day/night rhythm, e.g., nightshift worker, or normal bed time past midnight.
8. Subject has been diagnosed with sleep-related breathing disorder.
9. Subject has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 60 days before the planned first dose of study drug, or has participated in 2 or more clinical studies in the previous 1 year, or is currently enrolled in an investigational study.
10. Subject is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug.
11. Subject has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at Screening.
12. Subject has a history of human immunodeficiency virus (HIV) antibody positive, or tests positive for HIV at Screening.
13. Subject has a history of drug or alcohol abuse or dependence according to DSM-IV criteria, except nicotine or caffeine, within 6 months before Screening.
14. Subject has positive test result(s) for alcohol or drugs of abuse (including barbiturates, methadone, opiates, cocaine, cannabinoids, amphetamine/methamphetamine, and ecstasy) at Screening.
* Subjects with a positive alcohol or drug screen at Screening may have the test repeated once during the screening phase, based on the investigator's discretion. This determination, and the reason for permitting a repeat test, must be recorded in the subject's source documents and initialed by the investigator. A positive, repeat alcohol screen is exc

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>- Latency to persistent sleep (minutes)<br /><br>- Total sleep time (minutes)<br /><br>- Time spent awake (minutes)<br /><br>- Sleep efficiency (%)<br /><br>- Total time spent in Deep sleep (duration of slow wave sleep) (minutes)</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- PSG secondary endpoints<br /><br>Time in bed (minutes)<br /><br>Sleep onset latency (minutes)<br /><br>Number of awakenings (#)<br /><br>Time to REM sleep onset (minutes)<br /><br>Duration of REM sleep (minutes)<br /><br>Duration of Stage 1 Sleep (minutes)<br /><br>Duration of stage 2 Sleep (minutes)<br /><br>Number of REM blocks (#)<br /><br><br /><br>- Safety<br /><br>ECG<br /><br>Vital signs<br /><br>Clinical chemistry / hematology<br /><br><br /><br>- Depressive symptoms<br /><br>IDS-SR30<br /><br><br /><br>- Suicidal ideation<br /><br>C-SSRS<br /><br><br /><br>- Next day residual effects<br /><br>VAS Sleepiness<br /><br>VAS Bond and Lader<br /><br>Saccadic eye movements<br /><br>Body Sway<br /><br><br /><br>- Cortisol level in saliva</p><br>